ideasIdea
Use imaging to find the window when tumour blood vessels are working properly
Low doses of anti-blood-vessel drugs briefly make tumour vessels work better, which helps immune cells and other drugs get in. Scans can find that window for each patient.
Vascular normalisation after low-dose anti-angiogenic therapy is transient and dose-dependent, and DCE-MRI or perfusion CT can measure it patient by patient. Current anti-angiogenic and checkpoint combinations use fixed high doses and fixed schedules, so many patients are likely dosed outside their own normalisation window. Imaging-guided scheduling is a trial design intervention with existing drugs.
Hypothesis
Timing checkpoint or cytotoxic administration to an imaging-defined perfusion peak increases intratumoural drug delivery and T-cell infiltration compared with fixed scheduling.
Rationale
Normalisation is well documented in human rectal and glioblastoma studies where perfusion improvement correlated with outcome. Scheduling is free, and imaging endpoints read out in days rather than months.
What would test it
A randomised imaging-guided versus fixed-schedule window trial with intratumoural drug concentration or CD8 density as the primary endpoint in an accessible tumour.
Maturity
early clinical
Who has to act
clinic
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.